ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3078G>C (p.Trp1026Cys)

dbSNP: rs876660869
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001247764 SCV001421205 likely pathogenic Ataxia-telangiectasia syndrome 2022-07-29 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 971880). This missense change has been observed in individual(s) with ataxia-telangiectasia (PMID: 23726790, 28126470). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 1026 of the ATM protein (p.Trp1026Cys).
Sema4, Sema4 RCV002255639 SCV002535323 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-20 criteria provided, single submitter curation
Ambry Genetics RCV002255639 SCV003866495 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-14 criteria provided, single submitter clinical testing The c.3078G>C variant (also known as p.W1026C) is located in coding exon 20 of the ATM gene. This change occurs in the first base pair of coding exon 20. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). This alteration was detected in one breast cancer patient from a South African cohort (Eygelaar Det al, Sci Rep 2022 01;12(1):802). This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003469477 SCV004209411 likely pathogenic Familial cancer of breast 2024-03-22 criteria provided, single submitter clinical testing

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